Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Precision Medicine Phase 2 Option 1

NCT04602806 | Active Not Recruiting

• 1 other identifier: W81XWH-18-2-0042
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 5

Brief Summary

This study is being conducted to validate early and ultra-early blood-based and novel imaging biomarkers of Diffuse Axonal Injury (DAI), Microvascular Injury (MVI), and neuroinflammation that may serve as predictive and pharmacodynamic biomarkers in a new cohort of moderate-severe TRACK-TBI subjects. The study team will enroll a cohort of moderate to severe TBI subjects (N=50), stratified according to VA/DoD criteria for these injury severities through the existing TRACK-TBI network sites to obtain novel advanced neuroimaging and more frequent biomarker sampling. Subjects will be assessed over 3 months.

Conditions

Traumatic Brain Injury

Keywords

Traumatic Brain Injury; Biomarkers; Neuroimaging; Psychological Health; Concussion

Outcome Measures

Primary Outcomes (12)

• Blood Specimen for Analysis of Biomarkers

  Using advanced blood-based assay platforms, levels of blood biomarkers neurofilament light chain (NfL), Tau, Interleukin 6 (IL6), Interleukin (IL10), and Tumor Necrosis Factor (TNF) will be measured to validate their utility as early predictive and pharmacodynamic biomarkers for Diffuse Axonal Injury (DAI), Microvascular Injury (MVI), and Neuroinflammation. In addition, Ubiquitin C-terminal Hydrolase L1 (UCH-L1)/Glial fibrillary acidic protein (GFAP) markers will also be assayed for comparison. All biomarkers will be measured in picograms/milliliter (pg/mL).

  < 6 hours from the time of TBI

• Blood Specimen for Analysis of Biomarkers

  Using advanced blood-based assay platforms, levels of blood biomarkers neurofilament light chain (NfL), Tau, Interleukin 6 (IL6), Interleukin (IL10), and Tumor Necrosis Factor (TNF) will be measured to validate their utility as early predictive and pharmacodynamic biomarkers for Diffuse Axonal Injury (DAI), Microvascular Injury (MVI), and Neuroinflammation. In addition, Ubiquitin C-terminal Hydrolase L1 (UCH-L1)/Glial fibrillary acidic protein (GFAP) markers will also be assayed for comparison. All biomarkers will be measured in picograms/milliliter (pg/mL).

  12 hours from the time of TBI

• Blood Specimen for Analysis of Biomarkers

  Using advanced blood-based assay platforms, levels of blood biomarkers neurofilament light chain (NfL), Tau, Interleukin 6 (IL6), Interleukin (IL10), and Tumor Necrosis Factor (TNF) will be measured to validate their utility as early predictive and pharmacodynamic biomarkers for Diffuse Axonal Injury (DAI), Microvascular Injury (MVI), and Neuroinflammation. In addition, Ubiquitin C-terminal Hydrolase L1 (UCH-L1)/Glial fibrillary acidic protein (GFAP) markers will also be assayed for comparison. All biomarkers will be measured in picograms/milliliter (pg/mL).

  24 hours from the time of TBI

• Blood Specimen for Analysis of Biomarkers

  Using advanced blood-based assay platforms, levels of blood biomarkers neurofilament light chain (NfL), Tau, Interleukin 6 (IL6), Interleukin (IL10), and Tumor Necrosis Factor (TNF) will be measured to validate their utility as early predictive and pharmacodynamic biomarkers for Diffuse Axonal Injury (DAI), Microvascular Injury (MVI), and Neuroinflammation. In addition, Ubiquitin C-terminal Hydrolase L1 (UCH-L1)/Glial fibrillary acidic protein (GFAP) markers will also be assayed for comparison. All biomarkers will be measured in picograms/milliliter (pg/mL).

  Day 2 from the time of TBI

• Blood Specimen for Analysis of Biomarkers

  Using advanced blood-based assay platforms, levels of blood biomarkers neurofilament light chain (NfL), Tau, Interleukin 6 (IL6), Interleukin (IL10), and Tumor Necrosis Factor (TNF) will be measured to validate their utility as early predictive and pharmacodynamic biomarkers for Diffuse Axonal Injury (DAI), Microvascular Injury (MVI), and Neuroinflammation. In addition, Ubiquitin C-terminal Hydrolase L1 (UCH-L1)/Glial fibrillary acidic protein (GFAP) markers will also be assayed for comparison. All biomarkers will be measured in picograms/milliliter (pg/mL).

  Day 3 from the time of TBI

• Blood Specimen for Analysis of Biomarkers

  Using advanced blood-based assay platforms, levels of blood biomarkers neurofilament light chain (NfL), Tau, Interleukin 6 (IL6), Interleukin (IL10), and Tumor Necrosis Factor (TNF) will be measured to validate their utility as early predictive and pharmacodynamic biomarkers for Diffuse Axonal Injury (DAI), Microvascular Injury (MVI), and Neuroinflammation. In addition, Ubiquitin C-terminal Hydrolase L1 (UCH-L1)/Glial fibrillary acidic protein (GFAP) markers will also be assayed for comparison. All biomarkers will be measured in picograms/milliliter (pg/mL).

  Day 5 from the time of TBI

• Blood Specimen for Analysis of Biomarkers

  Using advanced blood-based assay platforms, levels of blood biomarkers neurofilament light chain (NfL), Tau, Interleukin 6 (IL6), Interleukin (IL10), and Tumor Necrosis Factor (TNF) will be measured to validate their utility as early predictive and pharmacodynamic biomarkers for Diffuse Axonal Injury (DAI), Microvascular Injury (MVI), and Neuroinflammation. In addition, Ubiquitin C-terminal Hydrolase L1 (UCH-L1)/Glial fibrillary acidic protein (GFAP) markers will also be assayed for comparison. All biomarkers will be measured in picograms/milliliter (pg/mL).

  Week 4 from the time of TBI

• Blood Specimen for Analysis of Biomarkers

  Using advanced blood-based assay platforms, levels of blood biomarkers neurofilament light chain (NfL), Tau, Interleukin 6 (IL6), Interleukin (IL10), and Tumor Necrosis Factor (TNF) will be measured to validate their utility as early predictive and pharmacodynamic biomarkers for Diffuse Axonal Injury (DAI), Microvascular Injury (MVI), and Neuroinflammation. In addition, Ubiquitin C-terminal Hydrolase L1 (UCH-L1)/Glial fibrillary acidic protein (GFAP) markers will also be assayed for comparison. All biomarkers will be measured in picograms/milliliter (pg/mL).

  Week 6 from the time of TBI

• Blood Specimen for Analysis of Biomarkers

  Using advanced blood-based assay platforms, levels of blood biomarkers neurofilament light chain (NfL), Tau, Interleukin 6 (IL6), Interleukin (IL10), and Tumor Necrosis Factor (TNF) will be measured to validate their utility as early predictive and pharmacodynamic biomarkers for Diffuse Axonal Injury (DAI), Microvascular Injury (MVI), and Neuroinflammation. In addition, Ubiquitin C-terminal Hydrolase L1 (UCH-L1)/Glial fibrillary acidic protein (GFAP) markers will also be assayed for comparison. All biomarkers will be measured in picograms/milliliter (pg/mL).

  3 Months from the time of TBI

• 3 Tesla Brain Structural and Functional Magnetic Resonance Imaging (MRI)

  This study aims to validate early and ultra-early novel imaging biomarkers in the acute phase after injury. In addition to volumetrics, Diffuse Tensor Imaging (DTI) and Resting State Functional Magnetic Resonance Imaging (rs-fMRI), the MRI protocol will incorporate novel imaging measures of axonal density using neurite density index (NDI) from Neurite Orientation Dispersion And Density Imaging (NODDI) analysis of multi-shell diffusion MRI, cerebral blood flow using Arterial Spin Labeled (ASL) perfusion, and neuroinflammation using free water content isotropic diffusion fraction (FISO) from NODDI analysis of multi-shell diffusion MRI.

  Within 24-48 hours from the time of TBI

• 3 Tesla Brain Structural and Functional Magnetic Resonance Imaging (MRI)

  This study aims to validate early and ultra-early novel imaging biomarkers in the acute phase after injury. In addition to volumetrics, Diffuse Tensor Imaging (DTI) and Resting State Functional Magnetic Resonance Imaging (rs-fMRI), the MRI protocol will incorporate novel imaging measures of axonal density using neurite density index (NDI) from Neurite Orientation Dispersion And Density Imaging (NODDI) analysis of multi-shell diffusion MRI, cerebral blood flow using Arterial Spin Labeled (ASL) perfusion, and neuroinflammation using free water content isotropic diffusion fraction (FISO) from NODDI analysis of multi-shell diffusion MRI.

  2 Weeks from the time of TBI

• 3 Tesla Brain Structural and Functional Magnetic Resonance Imaging (MRI)

  This study aims to validate early and ultra-early novel imaging biomarkers in the acute phase after injury. In addition to volumetrics, Diffuse Tensor Imaging (DTI) and Resting State Functional Magnetic Resonance Imaging (rs-fMRI), the MRI protocol will incorporate novel imaging measures of axonal density using neurite density index (NDI) from Neurite Orientation Dispersion And Density Imaging (NODDI) analysis of multi-shell diffusion MRI, cerebral blood flow using Arterial Spin Labeled (ASL) perfusion, and neuroinflammation using free water content isotropic diffusion fraction (FISO) from NODDI analysis of multi-shell diffusion MRI.

  3 Months from the time of TBI

Secondary Outcomes (3)

• Glasgow Outcome Scale Extended (GOSE)

  2 Weeks from the time of TBI

• Glasgow Outcome Scale Extended (GOSE)

  6 Weeks from the time of TBI

• Glasgow Outcome Scale Extended (GOSE)

  3 Months from the time of TBI

Study Arms (1)

Moderate to Severe TBI Subjects

Adult patients (age 18-65y inclusive) presenting to the Emergency Department (ED) with a history of acute TBI as per American Congress of Rehabilitation Medicine (ACRM) Criteria (i.e., patient has sustained a traumatically-induced physiological disruption of brain function).

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This is a population-based TBI study. All patients presenting with traumatic brain injury and receive a head CT scan as part of standard care within 6 hours of injury are initially eligible.

You may qualify if:

• Age 18 - 65y inclusive
• History or evidence of TBI, according to DoD-VA criteria
• Glasgow Coma Scale (GCS) 3 - 15 after resuscitation in the ED
• Head CT with evidence of trauma-related abnormality (except for isolated epidural hematoma (EDH))
• Ability to undergo MRI within 48 hours of injury
• Ability to obtain informed consent from participant or Legally Authorized Representative (LAR) within 6 hours of injury
• Fluency in English or Spanish

You may not qualify if:

• Unstable respiratory or hemodynamic status
• Evidence of penetrating brain injury
• Isolated EDH as only trauma-related CT abnormality
• Systemic traumatic injury that would preclude participation in study, which is expected to result in long-term disability not related to TBI
• Evidence of serious infectious complications (sepsis, bacteremia, multilobar pneumonia)
• Acute ischemic heart disease (myocardial infarction or unstable angina)
• History of syncope or hypotension
• Systolic blood pressure (SBP) \< 90 mm Hg, Diastolic blood pressure (DBP)\< 40 mm Hg for longer than 5 minutes
• History or evidence of active malignancy
• History of pre-existing neurologic disorder, such as dementia, mild cognitive impairment, uncontrolled epilepsy, multiple sclerosis, strokes, brain tumors, prior severe TBI, or other disorder that may confound interpretation of MRI or neuropsychological results
• History of pre-existing disabling mental illness, such as major depression or schizophrenia
• History or evidence of chronic heart failure or chronic renal failure
• Low likelihood of follow-up (e.g., participant or family indicating low interest, residence in another state or country, unhoused or lack of reliable contacts)
• Women who are pregnant or breast-feeding
• Prisoners or patients in custody

Sponsors & Collaborators

• University of California, San Francisco: lead
• U.S. Army Medical Research and Development Command: collaborator

Study Sites (5)

University of California, San Francisco

San Francisco, California, 94110, United States

Location

University of Pennsylvania/Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (15)

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• Alsop DC, Detre JA, Golay X, Gunther M, Hendrikse J, Hernandez-Garcia L, Lu H, MacIntosh BJ, Parkes LM, Smits M, van Osch MJ, Wang DJ, Wong EC, Zaharchuk G. Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med. 2015 Jan;73(1):102-16. doi: 10.1002/mrm.25197. Epub 2014 Apr 8.

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• McCrea M, Kelly JP, Randolph C. Standardized Assessment of Concussion (SAC): Manual for Administration, Scoring and Interpretation. 2nd ed. Waukesha, WI: CNS Inc; 2000. [Google Scholar]

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  BACKGROUND

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  BACKGROUND

Related Links

• Access to FITBIR data will be according to FITBIR policies.

Biospecimen

Retention: SAMPLES WITH DNA

Plasma and Serum will be collected at each of the following time points: within 6 hours of injury, and again at 12h, 24h, 2d, 3d, 5d, 2w, 6w and 3m post-injury. DNA is collected only at Day 1 of the Baseline Visit.

MeSH Terms

Conditions

Brain Injuries, Traumatic; Psychological Well-Being; Brain Concussion

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Personal Satisfaction; Behavior; Head Injuries, Closed; Wounds, Nonpenetrating

Study Officials

• Geoffrey T Manley, MD, PhD

  University of California, San Francisco

  STUDY DIRECTOR

• Claudia S Robertson, MD

  Baylor College of Medicine

  STUDY DIRECTOR

• David O Okonkwo, MD, PhD

  University of Pittsburgh Medical Center

  STUDY DIRECTOR

• Ramon Diaz-Arrastia, MD, PhD

  University of Pennsylvania

  STUDY DIRECTOR

• Nancy R Temkin, PhD

  University of Washington

  STUDY DIRECTOR

• Pratik Mukherjee, MD, PhD

  University of California, San Francisco

  STUDY DIRECTOR

• Joseph T Giacino, PhD

  Harvard Medical School, Spaulding Rehabilitation Hospital

  STUDY DIRECTOR

• Murray B Stein, MD, MPH

  University of California, San Diego

  STUDY DIRECTOR

• Mike McCrea, PhD, ABPP

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• Ramesh Grandhi, MD, MS

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: October 26, 2020
• Study Start: June 1, 2021
• Primary Completion: November 11, 2022
• Study Completion (Estimated): April 9, 2030
• Last Updated: April 13, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will become available after study completion.
• Access Criteria: * All Research Collaborations with TRACK-TBI begins with a written request submitted to the TRACK-TBI Executive Committee. The Research Collaboration Proposal form is attached as Appendix 1 in the Research Collaboration Policy available on the TRACK-TBI website. * Access to FITBIR data will be according to FITBIR policies found at https://fitbir.nih.gov/jsp/about/policy.jsp

Locations

US (5)